Influence of hypercortisolemia on the acute-phase protein response to endotoxin in humans.

Abstract

The response to systemic infection includes the coordinated appearance of hepatic acute-phase proteins, the production of which may be influenced by a counterregulatory hormonal background. This study sought to assess the potential for hypercortisolemic conditions to influence fibrinogen kinetics and other acute-phase protein responses in humans with endotoxemia. Eleven hospitalized healthy male volunteers underwent two separate determinations of fibrinogen kinetics, one baseline and one after administration of endotoxin (2 ng/kg intravenously; lot EC-5). Seven volunteers were studied without hormonal manipulation and four in the presence of a hypercortisolemic background (hydrocortisone infusion, 3 micrograms/kg/min). Fibrinogen fractional synthetic rates were estimated from the incorporation of orally administered 15N-glycine, and fibrinogen, C-reactive protein, cortisol, tumor necrosis factor-alpha, and interleukin-6 levels were also determined. The presence of an antecedent hypercortisolemic background resulted in an attenuated interleukin-6 response, as well as decreased fibrinogen synthesis and C-reactive protein appearance. The current data suggest that glucocorticoid hormonal influences are of importance in the regulation of endotoxin-induced cytokine and acute-phase protein responses.